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Constitutive phosphorylation of cardiac myosin regulatory light chain prevents development of hypertrophic cardiomyopathy in mice

Author:
Yuan, Chen-Ching, Muthu, Priya, Kazmierczak, Katarzyna, Liang, Jingsheng, Huang, Wenrui, Irving, Thomas C., Kanashiro-Takeuchi, Rosemeire M., Hare, Joshua M., Szczesna-Cordary, Danuta
Source:
Proceedings of the National Academy of Sciences of the United States of America 2015 v.112 no.30 pp. E4138
ISSN:
0027-8424
Subject:
cardiomyopathy, heart, heart failure, mice, mutants, mutation, myosin, phenotype, phosphorylation, therapeutics
Abstract:
Genetic hypertrophic cardiomyopathy (HCM) is a debilitating disease affecting 1 in 500 of the general population, and there is no effective therapy to reverse or prevent its development and/or progression to heart failure. To inhibit a detrimental HCM phenotype induced by the D166V mutation of cardiac myosin regulatory light chain (RLC) in mice that also show reduced phosphorylation of endogenous cardiac RLC, constitutively phosphorylated D166V mutant mice were produced and tested. Our in-depth investigation of heart morphology, structure, and function of S15D-D166V mice provided evidence for the pseudophosphorylation-elicited prevention of the progressive HCM-D166V phenotype. This study is significant for the field of HCM, and our findings may constitute a novel therapeutic modality to battle hypertrophic cardiomyopathy associated with RLC mutations.
Agid:
3387283